Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis

OBJECTIVE The aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence. DESIGN Multiple-treatments meta-analysis of randomised controlled trials. PARTICIPANTS Patients with depression following stroke. INTERVENTIONS 10 antidepressants and placebo in the acute treatment of PSD. OUTCOME MEASURES The primary outcomes were the overall efficacy, defined as the mean change of the total depression score. The secondary outcome was the acceptability, defined as risk of all-cause discontinuation. These estimates as standardised mean differences or ORs with 95% CIs. RESULTS We identified 12 suitable trials, with data from 707 participants. All drugs were significantly more effective than placebo apart from sertraline, nefiracetam and fluoxetine. Most of the comparisons for acceptability revealed no significant differences except that paroxetine had significantly lower all-cause discontinuation than doxepin, citalopram and fluoxetine. Standardised mean differences compared with placebo for efficacy varied from -6.54 for the best drug (reboxetine) to 0.51 for the worst drug (nefiracetam). ORs compared with placebo for acceptability ranged from 0.09 for the best drug (paroxetine) to 3.42 for the worst drug (citalopram). For the efficacy rank, reboxetine, paroxetine, doxepin and duloxetine were among the most efficacious treatments, the cumulative probabilities of which were 100%, 85.7%, 83.2%, 62.4%, respectively. With respect to the acceptability rank, paroxetine, placebo, sertraline and nortriptyline were among the most acceptable treatments, the cumulative probabilities of which were 92.4%, 63.5%, 57.3%, 56.3%. CONCLUSION After weighing the efficacy and acceptability, we conclude that paroxetine might be the best choice when starting acute treatment for PSD, and fluoxetine might be the worst choice. TRIAL REGISTRATION NUMBER This systematic review has been registered in the Prospective Register of Systematic Review Protocols (PROSPERO) public database (CRD42017054741; http://www.crd.york.ac.uk/PROSPERO).